TABLE 1

NNK metabolic activation in the lung and NM of WT and TG mice

NNK metabolism in microsomal reactions and NNK-induced O⁶-mG formation in vivo were assayed as described under Materials and Methods. Rates of ketoaldehyde and ketoalcohol formation (mean ± S.D., n = 3) were determined with NNK at 10 μM. Each microsomal sample (three per group) was prepared from pooled tissues of four 3-month-old male mice. For DNA adduct analysis, tissues were obtained 4 h after NNK treatment (100 mg/kg, i.p.). The O⁶-mG/guanine ratios (mean ± S.D., n = 4) were determined for 2-month-old female mice. Values in parentheses indicate relative increases for TG mice, compared with WT mice.

Tissue	Strain	Product Formation In Vitro		DNA Adduct Formation In Vivo
Tissue	Strain	Ketoaldehyde	Ketoalcohol	DNA Adduct Formation In Vivo
		pmol · min⁻¹ · mg protein⁻¹		O⁶-mG/10⁶ guanine
Nasal mucosa	WT	275 ± 53	388 ± 80	309 ± 10
	TG	597 ± 12^{^a} (220%)	575 ± 46^{^b} (150%)	439 ± 40^{^a} (140%)
Lung	WT	2.9 ± 0.4	16.2 ± 2.2	11.4 ± 0.8
	TG	5.7 ± 0.4^{^a} (200%)	19.8 ± 4.0 (120%)	13.0 ± 0.3 (110%)

↵a P < 0.01, compared with WT mice (Student's t test).
↵b P < 0.05, compared with WT mice (Student's t test).